This invention relates to drugs for reducing the risk of breast cancer and methods of using them.
It is known that the risk of breast cancer is related to pregnancy and that certain estrogen compounds affect the risk of cancer. Such compounds have been administered to mice and to women.
One compound that has been tested is estriol as described in "Estriol Prevention of Mammary Carcinoma Induced by 7, 12-dimenthylbenzanthracene and Procarbazine" by Henry M. Lemon, Cancer Research, 35, 1341-1353, May 1975. Estriol, a naturally occurring major human pregnancy hormone, was shown in that article to be moderately effective in inhibiting the development of breast cancers induced by a carcinogenic chemical.
Two other compounds and their method of use were described in "Pathophysiologic Considerations in the Treatment of Menopausal Patients with Oestrogens; the Role of Ostriol in the Prevention of Mammary Carcinoma" by Henry M. Lemon, Acta Endocrinologica, 1980, Suppl. 233:17-27. Those drugs are 6 keto estradiol and estriol 3-methyl ether. They were shown to have a 30-50 percent lifetime effect in reducing the appearance of breast carcinoma in treated rats as compared to other rats receiving carcinogen at the same time.
In one test: (1) 26 percent of the rats developed cancer in 7 months and 63 percent in one year when treated with estriol and a carcinogen; and (2) 31 percent of rats developed cancer in 7 months and 61 percent in one year when treated with 6 keto estradiol. Several other related drugs tested at the same did not provide the same beneficial results.
In tests with the other drugs the rats: (a) were treated with the drug and the carcinogen; and (b) examined for percentage incidence of cancer at 7 months and one year. Some of the other drugs in the test and their results were: (1) tamoxifen with 78 percent incidence in 7 months and 89 percent in one year; (2) diethylstilbestrol with 88 percent incidence in 7 months and 100 percent in one year; (3) 17 alpha ethynyl estradiol 17 beta with 90 percent in 7 months and 100 percent in one year; and (4) 2-OH estradiol 17 beta with 78 percent in 7 months and 94 percent in one year.
The three drugs which were effective and the methods of treatment using them have the disadvantages of low effectiveness and/or toxicity.
It is known to increase retention in uterus tissue by conjugating drugs with 17 alpha ethynyl which has a high rate of retention in uterus nuclei. Moreover, estrogen, 11-beta methoxy 17 alpha ethynyl estradiol 17 beta, which is retained in breast tissue, is known in biochemical studies of breast cancer tissue. However, this estrogen has the disadvantage of being carcinogenic in animals. It is also known that some estrogens cause cell transformation in tissue culture.